Prevalence and determinants of resistant hypertension in the delta region of Egypt: A prospective observational study

Abstract

Background and Aims

Hypertension (HTN) is a leading cause of morbidity and mortality affecting about 30%–40% of the adult population in developed countries. Fewer data were published about the prevalence, sociodemographics, and clinical characteristics of the resistant hypertensive population in Egypt. Hence, our aim is to focus the attention on these determinants especially in the delta region of Egypt.

Methods

Data belonging to patients visiting our HTN clinic in the Cardiovascular Department, Tanta University Hospital, Gharbeyah Governorate, Egypt, were collected over 12 months, between January 1, 2022, and 31 December 31, 2022, and then carefully analyzed.

Results

We found that the prevalence of resistant hypertension (RHTN) in the delta region of Egypt was 18%. We noted more RHTN cases in older age, that is, mean ± Std. was 51.5 ± 13.24 and 62.1 ± 7.56 for non‐RHTN and RHTN, respectively. Also, the prevalence was higher in women representing about 54.4% of cases. Sixty‐two percent of the patients with RH were obese (mean ± Std. of body mass index was 30.7 ± 5.36 in HTN and 47.7 ± 30.3 in RHTN groups with p value <0.001). We found a significant relationship between chronic kidney disease, diabetes, and RHTN.

Conclusion

Control of HTN among the Egyptian population in the delta region was unsatisfactory and higher than rates published globally. RH was more obvious in women, elderly, obese population, and diabetic and chronic kidney disease patients. Excessive use of nonsteroidal anti‐inflammatory drugs, smoking, and high salt intake were clearly observed.

Key points

• Resistant hypertension (RHTN) is prevalent more than described in the literature.

• RHTN is strongly associated with hypertension‐mediated organ damage, so its management is essential on personal and community levels.

• Efforts should be done to diagnose pseudo‐RHTN using out‐of‐office blood measurement techniques.

1. INTRODUCTION

Hypertension (HTN) is a major worldwide health problem and is the leading cause of global morbidity and mortality, affecting about 30–40% of the adult population in the developed countries. ¹

In Egypt, HTN is highly prevalent and is estimated to affect about 26.3% of the population older than 25 years old. About two thirds of that hypertensive population has other cardiovascular risk factors leading to aggravated cardiovascular morbidity and mortality. ² They remain at high risk for developing hypertension‐mediated organ damage (HMOD) such as premature cardiovascular disease (CVD) and chronic kidney disease (CKD). ³

According to The ESC/ESH and NICE guidelines, ⁴ , ⁵ resistant hypertension (RHTN) is identified based on office systolic and diastolic BP exceeding 140/90 mmHg, respectively, despite the concurrent use of three or more different antihypertensive agents, one of them being a diuretic.

In addition, RHTN also comprises patients who meet the previous definition and whose blood pressure remains uncontrolled despite four or more maximal doses of antihypertensive medications and usually described as having refractory HTN. ⁶

Although exposed to higher risk of cardiovascular morbidity and mortality, fewer data are published about the resistant hypertensive population in Egypt regarding their prevalence, sociodemographics, and clinical characteristics. Hence, our aim is to shed light on these determinants especially in the delta region of Egypt hoping for better control and prevention of complication.

The Nile Delta is one of the largest river deltas in the world, covering about 240 km of Mediterranean coastline, and is home to about 40 million Egyptians. It is formed in Lower Egypt, where the Nile River spreads out and empties into the Mediterranean Sea.  ⁷ , ⁸

We think our article is the first to focus on this topic among the Egyptian population.

2. METHODS

This study is a single‐center observational prospective study, with a convenient sample of a systematic type. Data were collected over 12 months, starting from January 1, 2022, to 31 December 31, 2022. We included hypertensive patients visiting our outpatient clinic in the Cardiovascular Department at Tanta University Hospital, Gharbeyah Governorate, Egypt.

We included adult patients aged 18 years and more, previously diagnosed to have essential HTN. Essential HTN was defined according to ESC/ESH guidelines ⁴ as a systolic blood pressure that is persistently elevated ≥140 mmHg on two or more occasions, and/or a diastolic blood pressure persistently elevated ≥90 mmHg on two or more occasions.

We considered HTN to be resistant if patients were on three appropriate antihypertensive drugs, including diuretics in maximal tolerated doses and their blood pressure remained (≥140/90 mmHg). ⁴ We also included patients with controlled blood pressure (<140/90 mmHg) but with more than three different antihypertensive drugs and are considered resistant by the American Heart Association guidelines. ⁹

The daily clinic is attended by a senior resident and a teaching assistant who are well trained in blood pressure measuring techniques and is equipped with well‐calibrated mercurial sphygmomanometer and automatic digital device which was mainly used for home measurement of blood pressure for cases suspected to have pseudo‐HTN; a condition with elevated brachial artery pressure assessed indirectly with sphygmomanometer, in spite of a normal intra‐arterial pressure assessed invasively usually as a consequence of inaccurate measurement, incorrect drug choices or white‐coat effect. ¹⁰ , ¹¹

Assessment of Blood pressure was done According to The ESC/ESH guidelines in three different measures after at least 5 min of rest, in the sitting position with mercurial sphygmomanometer, validated and calibrated with cuffs appropriate to the brachial circumference, with a minimum interval of 5 min between them.

Out‐of‐office methods, ambulatory blood pressure monitoring and home blood pressure monitoring were used to rule out pseudo patterns.

We excluded patients who refused to participate in the study and patients under investigation for or diagnosed with secondary HTN, for example, aortic coarctation. Also, we excluded patients with pseudo‐RHTN.

In the First clinic visit, the following variables were collected:

• (1)Sociodemographics data: age, gender, body mass index (BMI) with obesity diagnosis (when BMI values > 30 kg/m²), ¹² level of education (illiterate or educated), marital status (single, married, divorced, or widow), working or not, type and sector of work (manual, government, private, and retired).
• (2) Lifestyle data: smoking, dietary habits, and physical activity.
• (3)Documented pre‐existing comorbidities and cardiovascular risk factors diagnosed following recommendation of the latest ESC guidelines ¹³ :
  • −Diabetes mellitus (DM): diagnosis based on hemoglobin A1c (HbA1c) > 6.5% and/or fasting plasma glucose > 126 mg/dL, or on an oral glucose tolerance test if still in doubt.
  • −Chronic kidney disease: diagnosis based on presence of abnormalities of kidney structure or function, present for >3 months, with health implications. Markers of kidney damage, especially kidney disease due to DM, are albuminuria (albumin‐to‐creatinine ratio) > 30 mg/g in spot urine specimens and glomerular filtration rate < 60 mL/min/1.73 m².
  • −Peripheral arterial disease (PAD), diagnosed with Ankle‐brachial index < 0.90, Duplex ultrasound, computed tomography angiography, and magnetic resonance angiography.
  • −Dyslipidemia, blood cholesterol > 200 mg/dL, LDL‐cholesterol > 100 mg/dL, and/or HDL‐cholesterol < 40 mmol/L.
  • −Obstructive sleep apnea (OSA), bronchial asthma, ischemic heart disease, arrhythmias, heart failure with reduced (HFrEF), and cerebral stroke.

• (4)Current medication: number, classes, and duration of used antihypertensive medication, for example, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers, calcium channel blockers, diuretics. Other related medications such as Statin and ASA, steroids, and nonsteroidal anti‐inflammatory drugs (NSAIDs). Adherence to antihypertensive medications was assessed using the Morisky questionnaire. ¹⁴
• (5)Laboratory investigation: we focused on serum creatinine, electrolytes, lipid profile, HBA1C, urinalysis, and electrocardiogram. The echocardiography: either done 3 months before or after the initial visit, for chamber quantification and ejection fraction (EF) estimation.
• (6)The risk of developing OSA was assessed using the Berlin questionnaire. ¹⁵
• (7)Statistical analysis was done online using DATAtab: Online Statistics Calculator. DATAtab e.U. Graz, Austria. URL: https://datatab.net

2.1. Ethical consideration

The study was approved by the Ethical Committee of the Faculty of Medicine, Tanta University, Egypt (Ethical Approval Code: 36264PR132/3/23).

3. RESULTS

A total of 1369 hypertensive patients were included. Of them, 1010 patients representing (73.7%) of the total population, had non‐truly RHTN, also known as HTN group or group I.

True RHTN affected 359 of the remaining patients (26.3%), who are referred to as group II (Figure 1).

Figure 1.

Percentage of patients in each group according to the pattern of hypertension.

As regard age, the non‐truly resistant HTN group has lower values for age (mean ± Std. = 51.52 ± 13.24) than the true RHTN group (mean ± Std. = 62.13 ± 7.56). The difference between HTN and RHTN with respect to age was statistically significant, p = <0.05 (Figure 2A).

Figure 2.

Box plotting showing mean and standard deviation for: (A) age, (B) body mass index (BMI) in the resistant (RHTN) and non‐resistant HTN groups. HTN, hypertension; RHTN, resistant hypertension.

Also, the non‐truly resistant HTN group has lower values for BMI (mean ± Std. = 30.71 ± 5.36) than the RHTN group (mean ± Std.= 47.77 ± 30.3), p ≤ 0.05 (Figure 2B).

The non‐RHTN group I has lower mean systolic blood pressure (mean ± Std. = 152.52 ± 7.51) than the RHTN group (mean ± Std. = 164.68 ± 14.41). This result is statistically significant with p ≤ 0.05 (Figure 2C). Also, the HTN group has lower mean diastolic blood pressure (mean ± Std. = 94.16 ± 4.85) than the RHTN group (mean ± Std. = 100.6 ± 6.71), and these values were statistically significant, p ≤ 0.05 (Table 1).

Table 1.

Age, BMI, systolic, and diastolic blood pressure in both groups.

Variable (mean ± Std.)	Group I HTN, N = 1010	Group II True RHTN, N = 359	p Valuea
Age	51.52 ± 13.24	62.13 ± 7.56	<0.05
BMI	30.71 ± 5.36	47.77 ± 30.3	<0.05
Systolic blood pressure	152.52 ± 7.51	164.68 ± 14.41	<0.05
Diastolic blood pressure	94.16 ± 4.85	100.6 ± 6.71	<0.05

Abbreviations: BMI, body mass index; HTN, hypertension; RHTN, resistant hypertension; Std, standard deviation.

^a A Χ ² test was performed. A p value less than 0.05 was considered significant.

As regard gender, the prevalence of RHTN is higher in women representing about 54.4% of cases, while the resting 45.6% of RHTN cases were male (p value ≤ 0.05). No statistical significance between the two groups was found regarding the level of education and employment (p value = 0.275 and 0.075, respectively; Table 2).

Table 2.

Sociodemographics comparison between the two groups.

Variable (mean ± Std.)	HTN, N = 1010		True RHTN, N = 359		p Valuea
	n	%	n	%
Women	764	75.6	195	54.4	<0.05
Men	246	24.4	164	45.6	<0.05
Educated	510	50.4	187	51.36	0.275
Married	897	88.8	333	92	<0.05
Employed	550	54	157.77	43.7	0.075

Abbreviations: HTN, hypertension; RHTN, resistant hypertension.

^a A Χ ² test was performed. A p value less than 0.05 was considered significant.

It was clear that diabetes is associated with a higher risk for HTN to be resistant. We found a positive relationship between RHTN and DM (39.8% in the HTN group and 60.1% in the RHTN group) and the overall high prevalence of DM among our study population. The RHTN population was significantly dyslipidaemic; 83% versus 21.5% in non‐truly resistant population (Table 3).

Table 3.

Risk factors and associated comorbidities in the two groups.

Variable (mean ± Std.)	HTN, N = 1010		True RHTN, N = 359		p Valuea
	n	%	n	%
DM	481	39.8	218	60.1	<0.05
CKD	30	30	54	15	<0.05
IHD	134	13	192	53	<0.05
HFrEF	86	8.5	54	15	0.240
Dyslipidemia	218	21.5	301	83	<0.05
Cerebral stroke	33	32	47	13	<0.05
PAD	50	5	39	11	0.229
OSA	44	4.3	63	17.5	0.467
Smoker	317	31.3	255	71	<0.05
Salty diet	454	45.2	305	85	<0.05

Abbreviations: CKD, chronic kidney disease; DM, diabetes mellitus; HFrEF, Heart failure with reduced ejection fraction; IHD, ischemic heart disease; OSA, obstructive sleep apnea; PAD, peripheral arterial disease.

^a A Χ ² test was performed. A p value less than 0.05 is considered significant.

RHTN is associated with more risk for HMOD. Among the patients with RHTN, 15% suffered CKD, 53% had ischemic heart disease, and 13% had history of cerebral stroke. The relationship between HFrEF, PAD, and OSA and the pattern of HTN was insignificant in our result with p value = 0.240, 0.229, and 0.467, respectively (Table 3).

In about 85% of the resistant hypertensive population, there were regular daily salty diets, for example, pickle and salty cheese, compared to 45% in the non‐resistant group. Smoking was more prevalent in the RHTN group, with longer duration and higher daily cigarette consumption (Table 3).

As regard drugs taken in addition to concurrent antihypertensive therapy, we found a large proportion of patients using NSAIDs as analgesics to control their dental, spine, and knee joint pain, and almost without physician prescription (20% of patients in the resistant group while only 9.1% in the non‐resistant group).

Adherence to antihypertensive medications was assessed using the Morisky questionnaire and self‐reporting of daily use of the prescribed dose of antihypertensive medication and its timing. We found that the percentage of non‐adherence was about 59.6% and 17.4% in HTN and RHTN groups, respectively. The percentage of non‐adherence was less in the RHTN group mostly because of more comorbidity and the patient's will to survive possible complications (Table 4).

Table 4.

Current drug therapy among resistant and non‐resistant hypertensive groups.

Variable (mean ± Std.)	HTN, N = 1010		True RHTN, N = 359		p Valuea
	n	%	n	%
Thiazide diuretic	327	32.3	359	100	<0.05
Beta‐blockers	448	44.3	210	58.4	<0.05
ACEI	581	57.5	157	43.7	<0.05
ARBS	817	80.8	219	61	<0.05
CCBs	729	72.1	317	88.3	<0.05
statins	114	11.2	301	83.8	<0.05
NSAIDs	92	9.1	251	70	<0.05
Steroids	23	2.2	39	5.5	<0.05
Non‐adherence	598	59.6	62	17.4	<0.05

Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; HTN, hypertension; NSAID, nonsteroidal anti‐inflammatory drug; RHTN, resistant hypertension.

^a A Χ ² test was performed. A p value less than 0.05 is considered significant.

4. DISCUSSION

Despite the increased risk associated with RHTN and despite data gathered from the studies conducted in countries with similar socioeconomic profiles, for example, Pakistan and India showed that the prevalence of RHTN is on a steady rise, ¹⁶ this condition has been poorly focused on in literature especially in Middle Eastern countries including Egypt.

The prevalence of RHTN among the Egyptian population in the delta region of Egypt is shown in our study population to be 18%. Surprisingly, This finding is higher than many other observational studies. ¹⁷ , ¹⁸ , ¹⁹ However, it goes concomitant with others, such as The Controlled Onset Verapamil Investigation of Cardiovascular Endpoints trial, where a similar prevalence of RH was recorded. ²⁰

We found that possible reasons for the higher prevalence of RH could be the different conditions of our study being conducted in a specialized HTN clinic in a university hospital. Our clinic assesses patients referred from other hospital departments for consultation about their HTN status, for example, chest department, vascular surgery, and many times as a part of preoperative evaluation.

Excluding pseudo‐resistance HTN is of great importance to avoid over treatment, complications, or any burden over the financial capacity of the health system. In our study, about one third (34%) of the total patients had pseudo‐RHTN. We found that the most common cause of pseudo‐RHTN is wrong measurement techniques, as we noted that many patients depend on general pharmacies to record their blood pressure without the appropriate precautions.

As regard age, we found that the risk of RHTN increases with age. The mean age in the non‐resistant group was 51.5 years (Std. ±13.24), while the mean age in the RHTN group was 62.1 (Std. ±7.56). This finding agreed with Sim et al. ¹⁹ and Black et al. ²⁰ and showed that patients above 60 were significantly more likely to develop RHTN.

Framingham study ²¹ data showed that old age is the main predictor of RHTN because of age‐related changes in blood vessels and higher frequency of all related comorbidities (e.g., obesity, DM, and CKD).

Unlike some studies that stated that RHTN is more common in males, ²² we found contrary that prevalence is slightly higher in women representing about 54.4% of cases, while the resting 45.6% of RHTN cases were male (p value ≤ 0.001), particularly after the age of 55 years. Our finding could be explained by the fact that women, versus men, are more likely to have a higher prevalence of comorbidities such as CKD (36.0% vs. 28.1) and obesity (62.1% vs. 38%). Additionally, post‐menopausal women are influenced by estrogen withdrawal that leads to alterations in mechanisms regulating the sympathetic nervous system, renin‐angiotensin‐aldosterone system, body mass, oxidative stress, endothelial function, and salt sensitivity; all associated with a crucial inflammatory state and influenced by genetic factors, ultimately resulting in cardiac, vascular and renal damage and HTN. ²³ It is worth mentioning that in most of the studies about HTN conducted in Egypt, women were more affected than men. ²⁴

The association between obesity (defined as BMI > 30 kg/m²) and RHTN was statistically significant in our study, where 62% of the patients with RHTN were obese compared to about 32% of the non‐resistant group. Mean ± Std. of BMI was 30.7 ± 5.36 in HTN and 47.7 ± 30.3 in RHTN groups with p value < 0.001. Our finding runs parallel to Bramlage et al., ²⁵ where most of the obese patients need four drugs to control their blood pressure. The high prevalence of obesity is a real threat to Egyptian society and runs the bell to the real need for lifestyle modification, low‐fat diet, and routine exercises to reduce the incidence of both obesity and HTN.

In about 85% of the resistant hypertensive population, there was high salt intake, expressed simply in the form of daily use of pickles and salty cheese, compared to 45% in the HTN group. We also observed that in most of the cases, excessive salt consumption is a family behavior.

Literature suggest high salty diet as the main culprit causing resistance to antihypertensive agents ²⁶ as salts nullify the effect of even the most ideal drug therapy. ²⁷

Regarding adherence, we relied on self‐reporting of daily use of antihypertensive medication as regards the prescribed dose and its timing. We found that the percentage of non‐adherence was about 59.68% and 17.46% in HTN and RHTN groups, respectively. Surprisingly, This ratio is still less than mentioned in some literature, where a retrospective analysis conducted in the United Kingdom and the Czech Republic showed lack of adherence to antihypertensive treatments in about 50% of resistant hypertensive patients. ²⁸

Also, we found a good doctor–patient relationship on many occasions that is clearly facilitated by communication through the new social media methods, especially Whatsapp. This, in turn, encourages the patient to adhere to their medication and facilitates giving them simple advice and guidance.

Our study contained 84 patients with renal impairment; of them, 54 patients have RHTN. We found a significant relationship between chronic kidney disease and RHTN, running in parallel to the previous epidemiological studies ²⁹ , ³⁰ that identified kidney disease both as a cause and consequence of RHTN.

It is worth mentioning that inappropriate combinations of antihypertensive drugs were uncommon in our study and usually due to patients' misunderstanding. This was more common in illiterates, who commonly duplicate two medications with the same active ingredient. This finding is vastly away from the result of Marquez et al., ³¹ who identified potentially inappropriate drug combinations in 51.3% of older patients, with over‐prescription reported in 27.8% and under‐prescription in 35%.

As regard drugs taken in addition to concurrent antihypertensive therapy, we found a large proportion of patients (20% of patients in the resistant group in comparison to only 9.1% in the non‐resistant group) using NSAIDs as analgesics to control their dental, spine, and knee joint pain, and mostly without physician prescription. This overuse of NSAID medications can lead to increased Blood Pressure and interfere with antihypertensive agents. ³² Such medications should be avoided or withdrawn in resistant hypertensive patients, or at least the lowest effective dose should be administered.

In agreement with other previous studies, ¹⁹ , ³³ we found positive relationship between RHTN and DM (39.8% in the HTN group and 60.1% in the RHTN) and the overall high prevalence of DM among our study population.

We think our results are good indicator of the status of RHTN in the delta region of Egypt, although it is collected from one center. Our results were limited by missing the higher socioeconomic levels that prefer to follow up in private clinics. We also relied on patient's self‐reporting for compliance with antihypertensive medications and dietary intake that may be influenced by personal behavior.

5. CONCLUSION

From the present study, we concluded that the level of awareness and control of HTN among the Egyptian population in the delta region was unsatisfactory and higher than rates published globally.

RHTN was more obvious in women, elderly, obese population, and diabetic and CKD patients. Excessive use of NSAIDs, smoking, and high salt intake were clearly observed.

Hence, efforts should be enhanced for strategies addressing those high‐risk resistant hypertensive populations to increase awareness and adherence. Strategies for Healthy diet, exercise, and weight reduction should be a priority in health programs.

5.1. Study limitation

This study is a single‐center prospective observational study. Higher prevalence of RH could be due to the different conditions of our study being conducted in a specialized HTN clinic in a university hospital. Office blood pressure measurements were only made in the morning and during clinic hours of 9 a.m. to 1 p.m., missing the physiological blood pressure curve's noontime peak.

AUTHOR CONTRIBUTIONS

All authors have read and approved the final version of the manuscript. Mohammed Elbarbary is the corresponding author and has a full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

TRANSPARENCY STATEMENT

The lead author Mohammed Elbarbary affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Elbarbary M, Shoeib O, El‐saied SB, Atlm RM, Alkassas A. Prevalence and determinants of resistant hypertension in the delta region of Egypt: A prospective observational study. Health Sci Rep. 2023;6:e1441. 10.1002/hsr2.1441

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author.